Visceral obesity, but not central obesity, is associated with cardiac remodeling in subjects with suspected metabolic syndrome.

BACKGROUND AND AIMS: Metabolic syndrome (MetS) is a cluster of multiple risk factors including central obesity that may lead to cardiac damage and cardiovascular events. We investigated whether visceral obesity induces cardiac structural and functional remodeling independently from central obesity and other risk factors in subjects with suspected MetS. METHODS AND RESULTS: We studied 229 participants with suspected MetS. Visceral fat area (VFA) was measured by bioelectrical impedance analysis. Left ventricular (LV) mass index, early diastolic velocity of mitral annulus (e'), and LV global longitudinal strain (GLS) were measured by echocardiography. Subjects were categorized into high and low VFA group (VFAh and VFAl). MetS was more prevalent in the VFAh than in the VFAl (p = 0.004). The VFAh had a higher waist circumference (WC) than the VFAl (p < 0.001). LV mass index was higher, but e' and GLS were lower in the VFAh than in VFAl (all p < 0.05). VFA was well correlated with blood pressure, fasting blood glucose, triglyceride, high-sensitivity C-reactive protein and adiponectin (all p < 0.05). VFA was correlated to LV mass index, e', and GLS (all p < 0.05) and was independently associated with GLS after adjustment for other risk factors, including WC (p = 0.005). CONCLUSIONS: Visceral obesity assessed by VFA was well correlated with parameters of MetS. Visceral obesity, but not central obesity measured by WC, was independently associated with structural and functional cardiac remodeling in subjects with suspected MetS. It suggests that visceral obesity should be considered as an important risk factor for cardiac damage in dysmetabolic subjects. TRIAL REGISTRATION: NCT02077530 (date of registration: November 1, 2013).

Lymphangioma Arising From the Ovary.

Primary lymphangioma arising from the ovary is a rare tumor, with only 24 cases reported to date. As it is often accompanied by ascites or recurrence, similar to a malignant tumor, an aggressive treatment approach is used for disease control. In this report, we describe a 75-year-old woman with a left ovarian lymphangioma that increased in size during the menopause period. Microscopic examination of the tumor showed thin-walled multilocular cystic spaces and immunoreactivity for D2-40, a specific marker for lymphatic endothelium, lining the cystic spaces. The patient has been doing well for 5 years postoperatively. Ovarian cystic lymphangioma should be included in the differential diagnosis of an ovarian cyst and long-term follow-up is recommended to exclude malignant behavior. We also summarize a total of 25 cases, including the case presented here.

Vertebral compression fractures may increase mortality in male patients with chronic obstructive pulmonary disease.

BACKGROUND: Vertebral compression fracture (VCF) is frequent in chronic obstructive pulmonary disease (COPD) patients. However, little is known about whether VCF affects mortality in COPD patients. OBJECTIVE: To investigate whether VCFs might increase death in COPD patients. METHODS: In this retrospective cohort study, we enrolled 254 COPD patients with a recent history of hospitalisation due to respiratory problems. Patients were assessed for VCF using quantitative morphometric analyses of lateral chest radiographs; 211 patients received follow-up examinations for 2 years. RESULTS: Of the 211 COPD patients analysed, 60 (28.4%) had VCF at enrolment. During the follow-up period, 33/60 (55.0%) patients with and 46/151 patients (30.5%) without VCF died (P = 0.003, log-rank test). Cox proportional hazard analysis revealed that VCF is an independent risk factor for death after adjusting for age, sex, body mass index, smoking, dyspnoea scale, forced expiratory volume in 1 sec (FEV1) and comorbidities (hazard ratio for VCF = 1.79, 95%CI 1.11-2.89, P = 0.02). CONCLUSION: VCF might be an independent risk factor for death in male COPD patients.

Effect of mycophenolic acid on proliferation of dermal papilla cells and induction of anagen hair follicles.

BACKGROUND: Mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil, has anti-inflammatory effects, and is widely used as an immunomodulatory agent. However, the beneficial effect of MPA in hair-loss disorders is not fully understood. AIM: To investigate the direct effect of MPA on dermal papilla cells (DPCs), and to examine the hair growth-stimulating effects of MPA topically applied to mouse skin. METHODS: Cultured DPCs were treated with various concentrations of MPA and analysed by MTT assay. Expressions of hair growth-related genes, including Wnt/ß-catenin pathway-related genes and cellular apoptosis-regulating genes, such as Bcl-2, Bax and caspase-9, were examined using reverse transcription (RT)-PCR and western blotting. The Wnt/extracellular signal-regulated kinase (ERK) pathway was analysed by western blotting. The effect of topically applied MPA on anagen hair follicle induction after microneedle (MN) treatment with or without minoxidil (MXD) was evaluated by histopathological examination and RT-PCR. RESULTS: MPA showed a promoting effect on DPC proliferation, which was associated with increased Axin2 transcription levels. In addition, phospho-ERK protein was detected in the MPA-treated DPCs. An increased Bcl-2/Bax transcript ratio contributed to cellular proliferation, and this was maintained in the MPA-treated environment. Topically applied MPA promoted anagen hair follicle induction in mice. The effect of MPA on hair follicles was compatible with that of MXD, and this effect was accelerated by MN treatment. CONCLUSIONS: MPA promotes proliferation of DPCs and induction of anagen hair follicles in mice. This finding raises the possibility that MPA could be used as a treatment option for hair-loss disorders.

Malignant mixed Müllerian tumors of the uterus: sonographic spectrum.

OBJECTIVE: To describe the sonographic findings for malignant mixed Müllerian tumors (MMMTs) of the uterus with particular emphasis on their features on saline contrast sonohysterography (SCSH) and color Doppler sonography, and to determine how they relate to pathological findings. METHODS: The SCSH and color Doppler findings in 29 histologically proven cases of uterine MMMT were reviewed retrospectively and their relationship to gross and histological findings were investigated. RESULTS: Of the 29 uterine tumors, 16 were located only in the corpus, nine only in the fundus and four in both the corpus and fundus. Mean tumor size was 5.4 cm. The most common appearance was a polypoid mass projecting into the endometrial cavity, found in 23 cases. Twenty-eight tumors had an irregular surface, which was papillary in 20 cases and lobulated in eight. Most appeared heterogeneously isoechoic (n = 16) or hypoechoic (n = 12), occasionally with a trabecular appearance, and they often had clefts or fissure-like cystic areas (n = 10), necrosis (n = 4) or hemorrhagic areas (n = 7). Myometrial invasion was present in 27 cases and dilatation of the endometrial cavity was seen in 11. Color Doppler sonography showed moderate to marked vascularity in 20 out of the 24 cases in which it was performed, with a mean resistance index of 0.41, and appeared as feeding (n = 15) or randomly dispersed (n = 9) vessels. CONCLUSIONS: Uterine MMMTs have distinct sonographic features that are related to pathological findings. Knowledge of the sonographic appearance of MMMTs may facilitate diagnosis.

Effects of self-ligating brackets on the surfaces of stainless steel wires following clinical use: AFM investigation.

In orthodontic treatment, the frictional force between the archwire and bracket reduces the effectiveness of orthodontic treatment. The frictional force is affected not only by the geometry of the self-ligating brackets but also by physical changes between the bracket slots and archwire surfaces during sliding movement. This study examined quantitatively the effect of self-ligating treatments on the surfaces of stainless steel (SS) archwires during tooth movement in vivo by atomic force microscopy. Orthodontic 0.019″ × 0.025″ SS archwires after clinical use with the first bicuspid-extraction treatment were employed using the Damon 3MX(®) SS self-ligating brackets, Clippy-C(®) ceramic self-ligating brackets, and Kosaka(®) SS brackets. Intact SS archwires were used as the control group. All SS archwires after clinical use showed severe scratches and significantly higher roughness caused by frictional interactions between the brackets and archwires (p < 0.0001 vs. control). The descending order of surface roughness was the SS archwires treated, with ceramic self-ligating brackets, with conventional SS brackets, and with SS self-ligating brackets (p < 0.001). These findings suggest that an orthodontic treatment with SS self-ligating brackets may require smaller orthodontic forces than that with ceramic self-ligating brackets or conventional SS brackets.

ABCG2 polymorphisms, 34G>A and 421C>A in a Korean population: analysis and a comprehensive comparison with other populations.

BACKGROUND AND OBJECTIVE: ABCG2, also known as Breast Cancer Resistance Peptide (BCRP) or mitoxantrone-resistant protein, is the second member of the G-family of ABC transporters. The frequencies of ABCG2 34G>A and 421C>A polymorphisms in a Korean population were assessed using a newly developed multiplex pyrosequencing method, and compared with the corresponding frequencies seen in other ethnic groups. METHOD: We designed a multiplex pyrosequencing method to simultaneously detect ABCG2 421C>A and 34G>A polymorphisms and analysed the allele frequencies of these polymorphisms in 250 Korean subjects. RESULTS: The results showed 100% concordance between single and multiplex pyrosequencing methods. We also validated the polymorphisms identified by pyrosequencing with a direct sequencing method using randomly selected samples. The allele frequencies of ABCG2 421C>A and 34G>A in the population tested were 0·298 and 0·190 respectively. The allele frequency of the 421C>A polymorphism is comparable to other Asian populations, including Japanese and Chinese. However, both frequencies are different from those of Caucasians and Africans. CONCLUSIONS: The multiplex pyrosequencing method used to detect two ABCG2 polymorphisms concurrently is a rapid and reliable genotyping method for the detection of important ABCG2 genetic polymorphisms. The ABCG2 34G>A and 421C>A polymorphisms are frequently found in the Korean population. The frequencies are similar to those seen in other Asian populations including Japanese and Chinese, but very different to those of Caucasian and African-American populations.

Cyclooxygenase-2 expression in human thyroid disease.

OBJECTIVES: Cyclooxygenase (COX)-2, which is the inducible form of the COX enzyme for prostaglandin synthesis and a key mediator of epithelial cell growth, has been shown to be up-regulated in gastrointestinal cancers. Additionally, regular intake of other non-steroidal anti-inflammatory drugs (NSAID) is known to decrease the incidence of these cancers. Therefore, the goals of the present study were to determine the possible involvement of COX-2 in human thyroid diseases. METHODS: We used immunohistochemical staining and Western blot analysis to characterize the expression of COX-2 proteins in thyroid tissues from 64 patients with thyroiditis, benign tumors, and malignant tumors with or without metastasis. Immunoreactivity scores were calculated by multiplication of the determined grades. RESULTS: COX-2 proteins were not expressed in normal thyroid tissues. However, each type of tumor tissue showed intense bands of COX-2 protein expression in Western blot analyses, and the immunoreactivity scores were 7.67+/-1.17 (SD) for thyroiditis, 7.87+/-0.9 for benign tumors, 7.53+/-1.53 for follicular cancer, 7.63+/-1.11 for papillary cancer without metastasis, and 7.17+/-1.55 for papillary cancer with metastasis. No significant differences were found in the levels of COX-2 expression between different tumor tissue types. CONCLUSION: No significant correlations were observed between clinical and/or pathological characteristics of thyroid tumors and the intensity of COX-2 protein expression. In addition, we found no difference in COX-2 protein expression between thyroiditis and thyroid tumors. Thus, up-regulation of COX-2 protein synthesis in human thyroid diseases does not appear to be of clinical significance.

Pad - a new self-collection device for human papillomavirus.

This study was designed to determine the accuracy and agreement of a self-collection method using pad for human papillomavirus (HPV) DNA. One hundred and thirty-four patients at university hospitals voluntarily participated in the accuracy study, and 314 volunteers participated in the agreement study at local clinics. DNA was extracted and amplified using HPV L1 consensus primers designed for the direct sequencing. In the accuracy study, all samples were probed via histological examinations. With regard to the detection of squamous intraepithelial lesion (SIL), self-collection pad sampling displays sensitivity, of 76.9%, and specificity, of 93.3%. Three hundred and fourteen self-collection pad samples and the concurrent physicians' samples showed a 97.8% agreement, with a Kappa value of 0.9200. A new self-collection pad for the detection of HPV DNA appears to constitute an easy, rapid, and convenient alternative method for the cervical cancer screening of many women with the virtue of being incredible readily accessible.

Concurrent chemoradiotherapy in patients with nasopharyngeal cancer: prognostic significance of low expression of bax.

A randomized trial has demonstrated that concurrent chemoradiotherapy (CRT) is superior to radiotherapy (RT) alone in locally advanced nasopharyngeal cancer (NPC). Our study comprise 35 patients with locally advanced NPC (stage I: 1, II: 12, III: 7, IV: 15) with 1 cycle of induction chemotherapy (5-fluorouracil 1,000 mg/m(2)/day and cisplatin 20 mg/m(2)/day, days 1- 4) followed by concurrent CRT starting on day 22. Concurrent CRT consisted of RT (70 Gy/35 fractions for 7 weeks) with cisplatin 20 mg/m(2)/day for 4 days on weeks 1, 4, 7 of RT. Complete response (CR) was achieved in 33 patients (94%). Four-year progression-free survival (PFS) and overall survival (OS) of all patients were 57% and 65%, respectively. In analysis of prognostic factors, low expression of bax was the most significant independent predictor of poor prognosis in both PFS (p=0.002) and OS (p=0.008). In conclusion, the outcome of patients treated with this combined therapeutical modality appears to be comparable with that of Intergroup 0099 trial with high CR rate. Low expression of bax was significantly associated with poor PFS and OS.

Increased expression of caveolin-1 and microvessel density correlates with metastasis and poor prognosis in clear cell renal cell carcinoma.

OBJECTIVE: To investigate the relationship of caveolin-1 expression and microvessel density (MVD), a reflection of angiogenesis, with metastasis and prognosis in patients with clear cell renal cell carcinoma (RCC). PATIENTS AND METHODS: Formalin-fixed, paraffin-embedded tissue sections of clear cell RCC from 67 patients who had undergone radical nephrectomy were stained immunohistochemically with specific antibodies against caveolin-1 and CD34. Caveolin-1 immunostaining was semi-quantitatively estimated based on the proportion (percentage of positive cells) and intensity. MVD was determined with CD34-stained slides. The expression pattern of caveolin-1 and MVD was compared with the clinicopathological variables. RESULTS: Eighteen patients had either synchronous or metachronous metastases and 11 died during the follow-up. Caveolin-1 intensity was significantly correlated with tumour size (P = 0.005), TNM stage (P = 0.028), M stage (P = 0.012), grade (P = 0.015), and metastasis (synchronous or metachronous; P < 0.001). The caveolin-1 proportion (P = 0.037) and MVD (P = 0.011) were significantly correlated with metastasis. MVD was correlated with caveolin-1 intensity (r = 0.385, P = 0.001) and caveolin-1 proportion (r = 0.388, P = 0.001). There was no difference in the expression of caveolin-1 and MVD between primary and metastatic sites. The survival of patients with higher caveolin-1 intensity was significantly worse than that of patients with lower caveolin-1 intensity. Multivariate analyses indicated that only M-stage was an independent prognostic factor for cancer-specific survival and caveolin-1 expression was not an independent factor. CONCLUSIONS: Increased expression of caveolin-1 and MVD is associated with metastasis and a worse prognosis in clear cell RCC. Caveolin-1 expression is correlated with MVD. These results suggest that caveolin-1 may be important in the progression of clear cell RCC and angiogenesis may be affected by caveolin-1 during the progression of RCC.

Long-term evaluation of mice model infected with Helicobacter pylori: focus on gastric pathology including gastric cancer.

BACKGROUND: Long-term evaluation of gastric pathology after H. pylori infection is very important in order to reveal its clinical implications, since debate still exists on the gastric carcinogenesis provoked by H. pylori infection in animal models. AIM: Either to evaluate the long-term outcome of H. pylori infection or to determine how H. pylori could provoke gastric cancer in the mice model. METHODS: Four-week-old specific pathogen free C57BL/6 mice (n = 115) were infected with SS1, the mouse-adapted H. pylori strain. After 4, 8, 16, 24, 36, 50 and 80 weeks of bacterial infection, the H. pylori-infected mice were sacrificed. RESULTS: After 80 weeks of infection, almost all the H. pylori-infected mice developed hyperplastic gastritis, but did not show any evidence of gastric adenoma, dysplasia or carcinoma. PCNA positive cells were most abundant after 50 weeks and tended to decrease thereafter up to 80 weeks, whereas apoptosis began to be noted 8 weeks after H. pylori infection, showing 7-8 apoptotic cells/high power field, and tending to increase as time passed. Normally observed neutral mucin decreased during the experiment, showing the most marked decrease 50 weeks after H. pylori infection. In contrast, acidic mucin was noted from 50 weeks after infection. CONCLUSION: The SS1-infected mouse seems to be a suitable animal model for H. pylori-related research, and H. pylori itself does not induce gastric cancer in normal wild-type mouse model following long-term exposure, which could be explained by the balance that exists between cell proliferation and apoptosis.

Effect of long-term administration of rebamipide on Helicobacter pylori infection in mice.

BACKGROUND: It has been suggested that chronic, persistent, uncontrolled inflammations in the stomach could provide the basic step for the beginning of carcinogenesis. One of the potential clinical applications of rebamipide is the inhibition of the immunoinflammatory response in gastric mucosa imposed by Helicobacter pylori. AIM: To determine the implications of long-term rebamipide treatment in H. pylori infection, we studied the underlying moleculo-pathological changes in gastric lesions in mice infected with H. pylori (SS1 strain), following this treatment. METHODS: C57BL/6 mice were sacrificed 24 and 50 weeks after H. pylori infection, respectively. Colonization rates of H. pylori, degree of gastric inflammation and other pathological changes including atrophic gastritis and metaplasia, serum levels of IL-1beta, TNF-alpha, IFN-gamma and IL-10, mRNA transcripts of various mouse cytokines and chemokines, and NF-kappaB binding activities, and finally the presence of gastric adenocarcinoma were compared between an H. pylori infected group (HP), and an H. pylori infected group administered with long-term rebamipide-containing pellet diets (HPR). RESULTS: Serum levels of IL-1beta, IFN-gamma and TNF-alpha, the gastric mucosal expression of ICAM-1, HCAM and MMP, and transcriptional regulation of NF-kappaB-DNA binding were all significantly decreased in the HPR group compared with the HP group. An RNase protection assay showed, in the rebamipide administered group, significantly decreased mRNA levels of apoptosis-related genes such as caspase-8, FasL, Fas, TRAIL and various cytokines genes such as IFN-gamma, RANTES, TNF-alpha, TNFR p75, IL-1beta. In the experiment designed to provoke gastric cancer through MNU treatment with H. pylori infection, the incidence of gastric carcinoma was not different in either group. However, long-term administration of rebamipide showed the advantage of decreasing precancerous lesions like chronic atrophic gastritis and showed molecular evidence of attenuation of proliferation. CONCLUSION: The long-term administration of rebamipide should be considered in the treatment of H. pylori since it demonstrated molecular and biological advantages like a lessening of gastric inflammation and a possible chemopreventive effect.

Expression of multidrug resistance-associated protein1,P-glycoprotein, and thymidylate synthase in gastric cancer patients treated with 5-fluorouracil and doxorubicin-based adjuvant chemotherapy after curative resection.

Both 5-fluorouracil and doxorubicin are commonly used agents in chemotherapy of gastric cancer in adjuvant setting as well as metastatic disease. In a variety of malignancies, high expression of multidrug resistance-associated protein1 and P-glycoprotein has been associated with resistance to doxorubicin, whereas 5-fluorouracil resistance has correlated with the level of thymidylate synthase expression. We evaluated the expression of multidrug resistance-associated protein1, P-glycoprotein, and thymidylate synthase using immunohistochemistry in 103 locally advanced gastric cancer patients (stage IB-IV) who underwent 5-fluorouracil and doxorubicin-based adjuvant chemotherapy after curative resection and investigated the association between their expression and clinicopathologic characteristics including prognosis of the patients. While high expression (> or =5% of tumour cells positive) of multidrug resistance-associated protein1 and P-glycoprotein was observed in 70 patients (68%) and 42 patients (41%), respectively, 65 patients (63%) had primary tumours with high expression (> or =25% of tumour cells positive) of thymidylate synthase. There was a significant association between multidrug resistance-associated protein1 and P-glycoprotein expression (P<0.0001) as well as P-glycoprotein and thymidylate synthase expression (P<0.0001). High multidrug resistance-associated protein1 and P-glycoprotein expressions were associated with well and moderately differentiated histology (P<0.0001 and P=0.03, respectively) and intestinal type (P<0.0001 and P=0.009, respectively). High multidrug resistance-associated protein1 expression correlated with lymph node metastasis (P=0.037), advanced stage (P=0.015), and older age (P=0.021). Five-year disease-free survival and overall survival of total patients were 55.2% and 56.2%, respectively, with a median follow-up of 68 months. There were no significant differences in disease-free survival and overall survival according to the expression of multidrug resistance-associated protein1 (P=0.902 and P=0.975, respectively), P-glycoprotein (P=0.987 and P=0.955, respectively), and thymidylate synthase (P=0.604 and P=0.802, respectively). Concurrent high expression of these proteins (high multidrug resistance-associated protein1/P-glycoprotein, high multidrug resistance-associated protein1/thymidylate synthase, high P-glycoprotein/thymidylate synthase) did not correlate with disease-free survival or overall survival. Even high expression of all three proteins was not associated with poor disease-free survival (P=0.919) and overall survival (P=0.852). In conclusion, high expression of multidrug resistance-associated protein1, P-glycoprotein, and thymidylate synthase did not predict poor prognosis of gastric cancer patients treated with 5-fluorouracil and doxorubicin-based adjuvant chemotherapy. A larger study including patients treated with surgical resection alone would be necessary.

Expression profile of histone deacetylase 1 in gastric cancer tissues.

Although histone deacetylases (HDACs) appear to play a crucial role in carcinogenesis, the expression status of HDACs in primary human cancer tissues has not yet been reported. In this study, we investigated the expression level of HDAC1 in 25 paired primary human gastric cancer (GC) tissues and corresponding normal tissues through semi-quantitative RT-PCR and immunoblot analysis. The HDAC1 expression pattern was also topologically examined through immunohistochemistry. Overexpression of HDAC1 mRNA was detected in 68% of GC tissues (17 of 25), and the relative density of HDAC1 mRNA in GC tissue was increased 1.8-fold versus the normal counterpart (P < 0.01). Elevated expression of HDAC1 protein was also detected in 61% of GC samples (11 of 18), which also showed an increased mRNA level of HDAC. Immunohistochemically, overexpression of HDAC1 was predominantly localized in the nuclei of most neoplastic cells, including embolic tumor cells, whereas normal glandular epithelial cells revealed only weak HDAC1 expression that was focal in distribution. Thus, the present study clearly demonstrates that HDAC1 is overexpressed in GC and probably plays a significant role in gastric carcinogenesis.

Glomus tumor of the stomach: CT findings.

We present the radiologic findings of gastric glomus tumors in two patients, in whom upper gastrointestinal series and computed tomography (CT) were primarily used for diagnosis. The diagnosis was surgically confirmed. Contrast-enhanced CT showed peripheral nodular or homogeneous strong enhancement in the arterial phase and prolonged enhancement in the delayed phase.

Expression of thymidylate synthase in gastric cancer patients treated with 5-fluorouracil and doxorubicin-based adjuvant chemotherapy after curative resection.

We evaluated the expression of thymidylate synthase (TS) in locally advanced gastric cancer patients treated with adjuvant chemotherapy after curative resection and investigated the association between TS expression and clinicopathologic characteristics including prognosis of the patients. TS expression was evaluated by immunohistochemical staining using TS106 monoclonal antibody in 103 locally advanced gastric cancer patients (stage IB-IV) who underwent 5-fluorouracil (5-FU) and doxorubicin-based adjuvant chemotherapy after curative resection. 65 patients (63%) had primary tumours with high TS expression (> or = 25% of tumour cells positive), and 38 patients (37%) demonstrated low TS expression (< 25% of tumour cells positive or no staining). High TS expression was associated with male gender (P = 0.002), poorly differentiated histology (P = 0.015), and mixed type in Lauren's classification (P = 0.027). There were no statistically significant differences in 4-year disease-free survival (60.0% vs. 57.2%, P = 0.548) and overall survival (59.6% vs. 59.3%, P = 0.792) between high-TS group and low-TS group. In conclusion, although high TS expression was associated with poorly differentiated histology and mixed type in Lauren's classification, it did not predict poor disease-free and overall survival in gastric cancer patients treated with 5-FU and doxorubicin-based adjuvant chemotherapy after curative resection. Further prospective studies including the evaluation of other biological markers associated with the resistance to 5-FU and doxorubicin are necessary.

Photopatch testing in seven cases of photosensitive drug eruptions.

OBJECTIVE: The most important goal in the management of photosensitive drug eruptions, as in other types of drug eruptions is identification of the causative drugs to prevent reexposure to them. CASE SUMMARIES: Seven patients whose lesions were mainly distributed on sun-exposed areas underwent laboratory tests, phototests, and photopatch tests with suspected drugs. Phototests were done with ultraviolet A (UVA), UVB, and visible light. Drugs used in the photopatch tests were usually prepared as 10% concentrations in petroleum base, which did not produce reactions in 10 control subjects, followed by irradiation of suberythema doses of UVA. Systemic provocation by oral administration of small doses of causative drugs with irradiation of suberythema doses of UVA was performed to confirm the results of skin tests in four patients. Two patients were not rechallenged with the causative drugs. None of the patients had systemic lupus erythematosus, porphyria, or pellagra. All showed positive reactions to photopatch testing. Systemic provocation confirmed the results of photopatch tests in four patients. The two patients who were not rechallenged had no recurrence of lesions. One patient ingested only one drug at the time of eruptions, and provocation or avoidance was not attempted. A photoallergic mechanism was considered in five cases. CONCLUSIONS: Although there is no information about the appropriate concentrations or vehicles for suspected drugs, photopatch testing could be reliable for identification of causes of photosensitive drug eruptions. Besides piroxicam (a well-known photosensitizer) and carbamazepine, isoniazid and triflusal were identified as the causes of the reactions.

Increased expression of cyclooxygenase-2 protein in human gastric carcinoma.

Gastric adenocarcinoma is one of the most common malignancies in the world, and yet little is known about its molecular process of development and progression. Recent studies have suggested that ingestion of nonsteroid anti-inflammatory drugs reduces the risk of colon cancer, presumably by inhibiting the cyclooxygenase (COX) enzyme. COX-2, one isoform of the COX enzyme, is the rate-limiting enzyme in prostaglandin synthesis, and the function of this enzyme is thought to relate to inflammatory processes and carcinogenesis. To understand the role of COX enzyme in gastric cancer, we measured COX-2 expression in 104 human gastric carcinoma tissues by immunohistochemical analysis. We obtained tissue specimens from 104 surgically resected gastric adenocarcinoma patients. We performed immunohistochemical stain for human COX-2 with polyclonal antibody in gastric carcinoma. After curative resection and extensive lymph node dissection, all patients received adjuvant chemotherapy containing 5-fluorouracil. Expression of COX-2 showed cytoplasmic staining, not only in cancer cells but also in precancerous lesions such as metaplastic and adenomatous cells. We confirmed up-regulation of COX-2 in gastric cancer tissues compared with normal paired mucosa using Western blot analysis. There was no correlation between clinicopathological characteristics of gastric cancer patients and intensity of COX-2 protein expression. This study indicates that COX-2 protein over-expression may contribute to an early event of gastric cancer development, and it further suggests that selective inhibition of COX-2 may provide a chemopreventive effect against gastric carcinogenesis.